1. Technical Field of the Invention
The present invention relates to a remarkably improved method for producing disodium 5xe2x80x2-guanylate (i.e., 5xe2x80x2-guanylic acid disodium salt, being hereinafter often abbreviated as xe2x80x9c5xe2x80x2-GMP2Naxe2x80x9d) and disodium 5xe2x80x2-inosinate (i.e., 5xe2x80x2-inosinic acid disodium salt, being hereinafter often abbreviated as xe2x80x9c5xe2x80x2-IMP2Naxe2x80x9d), both being known to be important as seasonings, drugs and the like in the form of mixed crystals, not a mere mixture thereof.
2. Related Art
5xe2x80x2-GMP2Na and 5xe2x80x2-IMP2Na, as has been described above, are important in the fields of seasonings or condiments, drugs and the like. However, when they need to be used in combination, it is extremely difficult to prepare a mixture with a given mixed ratio by simply powder-mixing their crystals together, due to differences in the properties and powder characteristics of the two kinds of crystals. In addition, handling of such a mixture involves a variety of difficulties.
Meanwhile, there have been known as methods for producing 5xe2x80x2-GMP2Na and 5xe2x80x2-IMP2Na in the form of mixed crystals, the following three methods: I.e., a 1st one is a method (as disclosed in Japanese Patent Publication No. 12914/1965) comprising the steps of dissolving 5xe2x80x2-GMP2Na and 5xe2x80x2-IMP2Na in an aqueous solution containing an organic solvent such as methanol or the like and obtaining mixed crystals (being hereinafter often abbreviated as xe2x80x9cI+G mixed crystalsxe2x80x9d) of 5xe2x80x2-GMP2Na and 5xe2x80x2-IMP2Na from the resulting solution, a 2nd one is a method (as disclosed in Japanese Patent Publications Nos. 16582/1979 and 4787/80) comprising the steps of dissolving 5xe2x80x2-GMP2Na and 5xe2x80x2-IMP2Na in water and obtaining I+G mixed crystals from the resulting solution by means of crystallization by cooling or concentrating, and a 3rd one is a method (as disclosed in Japanese Patent Publication No. 215494/1991 and Japanese Patent No. 2,770,470) in which a 5xe2x80x2-IMP2Na-containing aqueous solution is gradually added to a 5xe2x80x2-GMP2Na slurry solution at precipitating 5xe2x80x2-GMP2Na, whereby I+G mixed crystals are formed.
Incidentally, 5xe2x80x2-GMP2Na and 5xe2x80x2-IMP2Na are known to form a mixed crystal in such a manner that 5xe2x80x2-GMP2Na is incorporated into a crystal lattice of 5xe2x80x2-IMP2Na in an aqueous solution containing an organic solvent such as methanol or the like or a mere aqueous solution. An X-ray diffraction pattern of the mixed crystal is almost the same as that of 5xe2x80x2-IMP2Na. It is considered that 5xe2x80x2-GMP2Na having a similar chemical structure to that of 5xe2x80x2-IMP2Na enters a lattice of 5xe2x80x2-IMP2Na, and they maintain a stable condition by means of hydrogen bonding. A crystal of 5xe2x80x2-IMP2Na has a good crystal form, and an I+G mixed crystal having the same lattice has almost the same crystal form.
In order to obtain I+G mixed crystals by crystallization, although the above 1st method can achieve crystallization at a high recovery rate, it has the problem that it requires expensive explosion-proof facilities on an industrial scale because it uses an organic solvent, and therefore production costs increase. Further, in order to obtain a product (mixed crystals) having a desirable weight ratio of 5xe2x80x2-IMP2Na to 5xe2x80x2-GMP2Na (being hereinafter often abbreviated as xe2x80x9cI/G ratioxe2x80x9d) by the above 2nd method, concentrated drains and feed liquids must be controlled, and conditions for setting temperatures, pressures and like must be strictly controlled in the case of crystallization by concentrating, while in the case of crystallization by cooling, the composition of a crystallization solution (i.e., a solution (to be) subjected to crystallization) must be controlled more strictly because the composition of the crystallization solution tends to change continuously, and therefore, both cases have the problem that devices and control of processes become complicated. In the case of the above 3rd method, the starting raw materials, 5xe2x80x2-IMP2Na and 5xe2x80x2-GMP2Na, must be kept separate from each other, and there is the problem that the number of facilities increases in order to prevent 5xe2x80x2-IMP2Na and 5xe2x80x2-GMP2Na from mixing with each other before crystallization.
Problems to be Solved by the Invention
It is an object of the present invention to provide a method for producing 5xe2x80x2-GMP2Na which is difficult to handle due to the properties and powder characteristic of its crystals in particular and 5xe2x80x2-IMP2Na, in the form of crystals which are easy to handle, that is, I+G mixed crystals having a given I/G ratio, under simple process control and with inexpensive facilities with the I/G ratio being controlled easily.
Means to Solve the Problem
The present inventors have made extensive and intensive studies to improve conventionally known crystallization methods of I+G mixed crystals, which methods involve complicated or intricate control and processes. Consequently, they have found that I+G mixed crystals with a given I/G ratio and stable quality can be deposited or precipitated by carrying out crystallization under constant temperature conditions that are industrially easy to control, more specifically, that the above object can be achieved by feeding a mixed feed solution of 5xe2x80x2-IMP2Na and 5xe2x80x2-GMP2Na with a high concentration which will become supersaturated at the temperature of the solution charged in the below-described crystallization bath (in the present specification, the term xe2x80x9ccharged solutionxe2x80x9d or xe2x80x9csolution chargedxe2x80x9d is used in such a sense that it includes xe2x80x9ccharged slurryxe2x80x9d or xe2x80x9cslurry chargedxe2x80x9d (in the broad sense)) into the crystallization bath (lower-temperature bath) kept at a constant temperature which is lower than the temperature of the mixed feed solution, whereby I+G mixed crystals are deposited from the mixed solution of 5xe2x80x2-IMP2Na and 5xe2x80x2-GMP2Na due to the difference in solubility which is, in turn, ascribable to the difference in temperature. The present invention has been completed based on these findings.
Accordingly, the present invention relates to a method for producing mixed crystals of disodium 5xe2x80x2-guanylate and disodium 5xe2x80x2-inosinate which comprises feeding a mixed solution of disodium 5xe2x80x2-guanylate and disodium 5xe2x80x2-inosinate which solution will become supersaturated at the below-mentioned constant temperature, to a solution or slurry of disodium 5xe2x80x2-guanylate and disodium 5xe2x80x2-inosinate charged in a crystallization bath (lower-temperature bath) and kept at a constant temperature, whereby mixed crystals of disodium 5xe2x80x2-guanylate and disodium 5xe2x80x2-inosinate are deposited from the mixed solution of disodium 5xe2x80x2-guanylate and disodium 5xe2x80x2-inosinate.